The lifetime risk of cancer will be quantified among 125,000 United States atomic veterans who participated at one or more of the 230 aboveground atmospheric nuclear weapons tests at the Nevada Test Site or the Pacific Proving Ground between 1946 and 1958. Reliable estimates of radiation dose for individual atomic veterans will be made which were not possible in previous investigations. Advances in dose reconstruction methods will permit dose-response evaluations and risk quantification. New knowledge will be sought on specific cancer risks following protracted low-dose exposure to external and internal radiation, including the inhalation and ingestion of plutonium, uranium and radioactive fission products. Previous studies identified excesses of leukemia and several other cancers, but reliable estimates of radiation dose were not possible. The hypothesis to be tested is that chronic low-dose radiation exposure some 50 to 60 years ago can be linked to increases in leukemia and other diseases, including coronary heart disease. An additional 20 years of mortality data will enhance our ability to uncover any radiation-related risks among military personnel present at one or more of the seven atmospheric test series with the highest recorded exposures, i.e., CASTLE, GREENHOUSE, REDWING, UPSHOT- KNOTHOLE, PLUMBBOB, CROSSROADS and HARDTACK I. New developments in statistical methodologies will be applied to account for the uncertainty in the estimated radiation doses. Preliminary estimates indicate a broad range of doses from minimal (<1 mSv or 0.10 rem) to over 900 mSv (or 90 rem). All causes of death will be evaluated, and radiation doses will be reconstructed for all veterans who died of leukemia and cancers of the thyroid, salivary gland, male breast, liver and bone, i.e., for cancers previously reported to be increased, as well as on a 1% random sample of the entire cohort. The focus will be on leukemia for which over 1,000 cases are estimated to have occurred. The proliferating use of CT x-ray as well as radionuclide imaging (e.g., PET scans) highlights the need for accurate estimates of lifetime radiation risk following chronic low-dose exposures for which cumulative population doses could be substantial. The evaluation of risks among persons with exposure to radioactive substances assumes greater importance as society debates expansion of nuclear energy and associated nuclear waste and the possibility of terrorist attacks with "dirty bombs." The proposed study thus provides a unique, timely and cost-effective opportunity to address important public health and societal issues, taking advantage of detailed radiation dose and veteran data already developed by the Department of Defense over the past 30 years. Finally, the proposed project is important to veterans and their families in providing a better understanding of the health risks associated with their prior military service. Public Health Relevance: Atomic veterans who participated in any of the 230 atmospheric nuclear weapons tests at the Nevada Test Site and the Pacific Proving Ground between 1946 and 1958 could have been exposed to various types of radiation including gamma rays, alpha particles and intakes of radioactive substances such as plutonium, uranium and fallout products. Results of this study will provide new knowledge on the lifetime risk of cancer following relatively low-dose exposures received gradually over time. Such information is helpful in understanding the very long-term consequences of radiation exposures and assumes greater importance today in light of the proliferating use of CT x-ray and radionuclide imaging, the possible expansion of nuclear power, and concerns over nuclear waste disposal and terrorist attacks with "dirty bombs."